Toste has found a mother lode of new and unique gold-catalyzed reactions by applying

Einstein's theory of relativity to the rare and precious metal.

Catalysts are metals that speed up chemical reactions, such as when the platinum in a car's
catalytic converter instantly converts polluting engine exhaust to oxygen, nitrogen, carbon
dioxide and water.
Dean Toste, a UC Berkeley associate professor of chemistry, was one of the first chemists to
experiment with gold as a catalyst. He opened the door for others interested in gold's
versatility and in the potential to generate chemicals of interest for the chemical and
pharmaceutical industry more efficiently and using less toxic precursors.
"This is a really hot area," Toste said. "If you look at the most-cited articles in the Journal of
the American Chemical Society, many are about gold catalysis.
"With this class of gold catalysts, you can develop a number of unprecedented reactions that
have never been seen before."
In a review article appearing in today's (March 22) issue of Nature, Toste discusses the new
field and proposes a new theory for why gold has such unusual, and practical, catalytic
properties. So far, the hypothesis has successfully predicted the behavior of gold catalysts in
new chemical reactions.
"Our hypothesis really allows us to approach catalysis in a new way, melding the two fields of
theoretical chemistry and synthetic chemistry," Toste said.
At the heart of his hypothesis is the special theory of relativity, proposed by Albert Einstein
102 years ago and typically thought of as applying only to cosmological questions. But late
UC Berkeley chemist Kenneth Pitzer showed some 70 years ago that the theory comes into
play in chemistry as well. Other researchers have used so-called relativistic quantum
mechanics to explain gold's yellow color and why mercury is a liquid instead of a solid.
Toste now takes this explanation a step further, crediting special relativity with making gold -
and perhaps the related and widely used catalyst platinum - act as both an acceptor and a
donor of electrons in a catalytic reaction. Typical metal catalysts do one or the other, but not
both.
One of the key tenets of relativity is that nothing can travel faster than the speed of light. The
reason for this is that objects become heavier, or more massive, the faster they go, with the
mass approaching infinity as the object approaches the speed of light.
In an atom, where electrons race around the nucleus like buzzing bees, the velocity of an
electron doesn't get anywhere near the speed of light until the atomic nucleus fills up with lots
of positively charged protons - the negatively charged electrons have to move faster to keep
from being pulled into the highly positive nucleus. This occurs in the transition metals of the
periodic table of elements, metals ranging from tantalum and tungsten to platinum and gold.
In a gold atom, with 79 protons in the nucleus, the 79 electrons whip around the nucleus at
about half the speed of light.
The net effect is that gold's electrons are much heavier and are pulled in closer to the
nucleus, lowering the energy levels and making the atom more compact. According to this
hypothesis, gold's s shells, which are its lowest energy spherically symmetric electron shells,
contract. This shields the electrons in outer, asymmetric p and d orbits from the nuclear
charge, allowing them to expand slightly. In gold, the contraction of the outermost (6s) shell
and the expansion of the next-inner (5p) shell reduces the energy difference between the two
to the equivalent of a photon of blue light. This allows gold to absorb blue light and, thus, look
yellow. Silver, because it exhibits a much less dramatic relativistic effect, is unable to absorb
any visible light and is totally reflective.
Toste proposes that this same shielding effect allows the more tightly bound s shell to easily
accept electrons from other molecules, while the partly shielded d shell can easily donate
electrons to a reaction.
Thus, gold is able to participate in reactions both as a donor and as an acceptor of electrons,
which makes it particularly useful in catalyzing reactions at carbon-carbon bonds, the
backbone of all organic molecules. According to Toste, a gold atom can attach to carbon
loosely, with a single bond or a double bond, allowing flexibility in reactions that can lead to
novel organic molecules.
Using this model, he has accurately predicted the products in various organic reactions. For
example, a gold atom attached to the chemical phosphine and dispersed homogeneously in a
liquid can efficiently convert alkynes to pyrroles, which are ring structures found in many
drugs. Gold-phosphine catalysis also can create an unusual carbon triangle called
cyclopropane that is used in industrial organic synthesis.
"We can make cyclopropanes without the need for explosive diazo compounds," Toste said.
Toste predicts that gold catalysts also will be very useful in producing chemicals with a
specific handedness, that is, a left-handed molecule, but not its right-handed or mirror image.
Such stereoselective reactions are becoming more important because many drugs come in
right- and left-handed forms, but only one form is effective in the body. The most efficient
synthesis would produce only the effective form, not its ineffective mirror image. He is tuning
the phospine attached to gold to affect this stereoselectivity.
"The future of gold catalysis still involves a lot of theoretical work, and we need to understand
more about how it works," Toste said. "But already, some of these reactions are being used by
medicinal chemists, and it's a really exciting field."
The coauthor with Toste on the Nature review is UC Berkeley graduate student David J.
Gorin.
The research was funded by the National Institute of General Medical Sciences of the
National Institutes of Health, and by Merck Research Laboratories, Bristol-Myers Squibb,
Amgen Inc., DuPont, GlaxoSmithKline, Eli Lilly & Co., Pfizer, AstraZeneca, Abbott, Boehringer
Ingelheim, Novartis and Roche. Toste is the Chevron Professor of Chemistry at UC Berkeley.